title: T-cell factor/β-catenin activity is suppressed in two different models of autosomal dominant polycystic kidney disease.
abstract: During murine kidney development, canonical WNT signaling is highly active in tubules until about embryonic days E16-E18. At this time, β-catenin transcriptional activity is progressively restricted to the nephrogenic zone. The cilial protein genes PKD1 and PKD2 are known to be mutated in autosomal dominant polycystic kidney disease (ADPKD), and previous studies proposed that these mutations could lead to a failure to suppress canonical WNT signaling activity. Several in vitro studies have found a link between cilial signaling and β-catenin regulation, suggesting that aberrant activity might contribute to the cystic phenotype. To study this, we crossed T-cell factor (TCF)/β-catenin-lacZ reporter mice with mice having Pkd1 or Pkd2 mutations and found that there was no β-galactosidase staining in cells lining the renal cysts. Thus, suppression of canonical WNT activity, defined by the TCF/β-catenin-lacZ reporter, is normal in these two different models of polycystic kidney disease. Hence, excessive β-catenin transcriptional activity may not contribute to cystogenesis in these models of ADPKD.
authors.affiliation: Department of Human Genetics, McGill University-Montreal Children's Hospital Research Institute, McGill University Health Centre Research Institute and McGill University, Montreal, Quebec, Canada.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Miller
authors.forename: Diana M
authors.initials: DM
authors.lastname: Iglesias
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rachel
authors.initials: R
authors.lastname: Corsini
authors.forename: LeeLee
authors.initials: L
authors.lastname: Chu
authors.forename: Inga
authors.initials: I
authors.lastname: Murawski
authors.forename: Indra
authors.initials: I
authors.lastname: Gupta
authors.forename: Stefan
authors.initials: S
authors.lastname: Somlo
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
authors.forename: Paul R
authors.initials: PR
authors.lastname: Goodyer
mesh_terms: D000367:Age Factors; D000818:Animals; D003560:Cysts / Q000209:etiology*; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050396:TRPP Cation Channels / Q000235:genetics; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051820:TCF Transcription Factors; D050396:TRPP Cation Channels; D051153:Wnt Proteins; D051176:beta Catenin; C495267:CTNNB1 protein, mouse